Download Immunoglobulin replacement therapy

Patient Guide to
Immunoglobin
Replacement Therapy
This booklet is to help you understand a little bit more about what is
happening to your health at the moment and what we can do to try
and help you stay well. We understand that coming to hospital can
be a worrying time and you probably have some questions about
your condition that you hadn’t thought of when you were last with us.
Some of the answers may be contained within the following pages.
You may also have more questions to ask after reading this and we are
always happy to answer any queries you have.
Contents
The immune system
4
Immunoglobulins
5
Immunodeficiency: primary and secondary
5
Treatment
7
Why do I need the treatment
7
Having your treatment
8
Treatment options
10
Differences between IV & SC treatment
11
Blood testing
12
Psychological treatment
12
Jeffrey Model Foundation
13
Glossary of terms
14
Useful websites
16
Contact us
17
3
The immune system
The immune system is the body’s natural defence mechanism, consisting
of various cells, tissues and organs and is our way of protecting ourselves
from harmful organisms such as bacteria, fungi and viruses. These are
also known as antigens or pathogens. When you come into contact with
them your body will try to defend itself and the Immune System is how it
goes about it.
White blood cells (also known as leukocytes) make up a very
important part of the immune system and have two main types:
1: Phagocytes: these are basically cells that swallow up and digest any
bugs or cells which have been identified as harmful. The most
common type is the Neutrophil.
2: Lymphocytes: there are two types of lymphocytes, which are B and
T cells. Both are responsible for recognising and remembering
antigens which you have come into contact with before. They are
more specialised in how they work and help you to become
“immune” to certain diseases.
Basic anatomy of immune system
Lymph
node
Thymus – involved in T-cell development and
maturation
Liver
Lymph nodes – site of antigen and lymphocyte
interaction and one of the sites of antibody
Lymph
production
vascular
Thymus
Spleen
Kidney
system
Liver – breaks down (metabolises) toxic
substances and contains immunologically active cells
Kidneys – maintain fluid balance within the body
and filters chemicals from blood into urine
Bone marrow – inner part of bone where immune
cells and antibodies are produced
Spleen – site of B cell maturation and where blood
cells, platelets and antigens are broken down
Lymph vascular system – carries antibodies and
antigens throughout the body
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Bone Marrow
Immunoglobulins
Immunoglobulins are a type of protein and an important part of the
immune system. They are made by B-cells and are also known as
antibodies. There are three main types:
1: Immunoglobulin M (IgM) antibodies are the first to react to the threat
of antigens and are important for the first few days of infection.
2: Immunoglobulin A (IgA) antibodies are found in the mucosal areas of
the body and protect those areas with a high antigen concentration
and where the physical barrier (mucous membrane) is less effective
than the skin. The nose, mouth, digestive tract, and eyes are all areas
where IgA can be found.
3: Immunoglobulin G (IgG) antibodies are perhaps the most important
of the antibodies and are found throughout the body. They are
produced in far higher quantities and can recognise and attack
particular antigens. Particular IgG antibodies will match up with the
antigens and help destroy them. It can also signal other immune cells
to come and help.
Immunodeficiency
People with immunodeficiencies are less able to fight infections as their
immune system is not working properly, either partially or not at all. They
generally get infections more frequently and will also tend to take longer
getting over them. The infections normally appear around the lungs
(chest infections), the nasal passages (sinusitis) or the gut (diarrhoea). In
the UK, roughly 5,000 people are thought to be affected, although this
figure is steadily rising with greater understanding of the condition.
If you have been diagnosed with an immunodeficiency you do not need
to panic. Most conditions that fall under the term can be managed very
successfully with medical treatment.
Some patients may only need to have regular check-ups or clinic visits to
have their blood tested. Others will need to take regular antibiotics to
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limit the number of infections they have been having. A few will need to
have essential antibodies replaced by intravenous (IV, which means into a
vein) or subcutaneous (under the skin) infusions. This helps to boost the
immune system to a level comparable with unaffected people. Some
children with a severely compromised immune system can have it
replaced with a healthy one by bone marrow transplantation. This is a
well understood and mostly successful procedure, however, its use in
adults is limited. New treatments, such as gene therapy, are also being
developed for some more severe forms of immunodeficiency.
Primary immunodeficiencies (PIDs) are immunodeficiencies that people
are born with or develop spontaneously later in life without any obvious
reason. There are many different types of primary immunodeficiencies
with varying degrees of severity. The causes are thought to be mostly
genetic and will depend on the gene or genes affected and the amount of
mutation present. About 20% of patients found to have a primary
immunodeficiency will also have a close family member affected, although
not necessarily with the same condition. There is a lot of research currently
trying to discover more about the causes of immunodeficiencies, some of it
carried out here at the Royal Free.
Secondary immunodeficiencies are those that are acquired
later on in life and can be due to infections, some types of
cancer or from certain drug therapies such as chemotherapy,
immunosuppression, antimalarial treatment or epileptic medication.
Important information about HIV – A lot of people when they
hear the term Immunodefieciency automatically think of HIV or
AIDS. This is a completely different condition, caused by a virus,
and is not the same. Primary immunodeficiencies are not related
to HIV or AIDS.
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Treatment
There is much that is still not understood about problems with the
immune system and consequently new treatments and research is being
carried out all the time to improve the quality of life for people with
immunodeficiencies. The new UCL Institute of Immunity and
Transplantation at the Royal Free will have an important focus on research
into primary immunodeficiency disorders to improve diagnosis and care.
The treatment for primary and secondary immunodeficiency is the same
and usually involves infusions of antibodies to replace those not already
present. This would typically be given straight into a vein (IVIg) or into
the subcutaneous layer of tissue around the abdomen or upper thigh
(SCIg). Treatment would either be on a day ward at a hospital or, if
appropriate, training can be given to carry out infusions at home. Many
patients find home therapy a convenient way to have treatment with
minimal disruption to their day-to-day lives.
There are a number of different manufacturers making immunoglobulin
replacement therapies and you may hear us refer to them as “products”.
Naturally occurring antibodies (specifically IgG) found in human blood
plasma are the essential components of all these products. This is
obtained from screened donors and purified using a lengthy and
complex filtering system to ensure that, as much as possible, any harmful
components are removed. The main way these products differ is in the
solution they are dissolved in and the concentration. For most patients,
one product will be as good as another.
Why do I need the treatment?
The term immunodeficiency means that your immune system is not
working fully and therefore needs help to fight off infections caused by
viruses and/or bacteria and/or fungi (pathogens). Usually your body
produces immunoglobulin (antibodies) all the time to help keep you well
but often an immunodeficient person is not able to do this and can
become easily unwell. The antibodies that should be present in blood
need to be replaced through infusions and this is where the term
“replacement therapy” comes from.
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As already mentioned, the replacement products are sourced from a
large amount of donors, which means they contain a wide range of
antibodies effective against most of the general pathogens within the
population. This does not mean, however, that you will now be
protected against all kinds of pathogens. At best, being on replacement
therapy will mean that you have a similar chance of catching common
infections as anyone else. This means it is vitally important you look after
yourself by maintaining good hygiene, taking regular exercise (especially
if you already have lung damage), eating a healthy diet and, most
importantly, not smoking.
Having your treatment
Before starting any treatment a doctor and one of the nurses will
explain to you what this involves, giving you a chance to ask any
questions you may have. If you are still unclear about anything, please
use the details given at the back of the booklet to contact us. We are
always happy to discuss issues relating to your treatment and
understand that this may be a bewildering time for you and your family.
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On the ward
Initially your treatment will be given on the Institute of Immunity and
Transplantation infusion ward on the second floor of the Royal Free Hospital
but may be transferred to your local hospital if you don’t live locally.
Once on the ward, one of the nurses will show you around and check
that we have your contact details and next of kin listed correctly. Before
you start your treatment one of our doctors will ask you to sign a
consent form confirming that you understand what the treatment is and
why it is necessary. They will also be able to answer any questions that
you may have.
The first few times you have the treatment it will take between 4-6
hours. This slow starting rate is to make sure you can tolerate the
infusion and will gradually be increased to a faster normal rate. You will
also be given a small dose of hydrocortisone, a steroid, on your first two
visits to lessen the effects of any potential reactions. We recommend that
you be collected or take a taxi home after these first few sessions. It is
important that you have breakfast and something to drink before your
infusion. Lunch and other drinks will be provided for you throughout the
day. Free Wifi is available on the ward during your stay.
Side effects
There is a possibility that you may have a slight reaction to the
product you are on, although this is not common. This could mean
feeling faint or dizzy, lower back pain, short of breath, itchiness or a
headache. Often, this will only happen the first few times you have an
infusion but occasionally it can continue. If so, we may consider
changing your immunoglobulin product. This is nothing to worry about.
It only means that your body is a little sensitive to that particular solution
and not to the essential ingredient (immunoglobulin) within it.
Infusion reactions can also occur if you have an active infection.
Sometimes we need to delay your infusion until your infection has been
treated. Please let us know if you are unwell when you are due to have
your infusion, so we can discuss whether to delay your infusions or not.
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Treatment options
The amount of monthly immunoglobulin is usually worked out by body
weight. There are two ways of having an immunoglobulin infusion: IV
(intravenous) or SC (subcutaneous) and both routes involve having the
same amount of immunoglobulin over the course of the month. Each
method is acceptable and has certain advantages over the other. The one
you decide on will depend on you personal preference and we would
support you whichever you choose. It is also possible to change from one
to the other at any time.
Intravenous infusions go directly into a vein in your arm or hand using a
small butterfly needle. We try to rotate the veins used so they can be
rested and kept working for as long as possible. Once established on a
suitable IV product, your treatment will typically take place every 3-4
weeks and should take about 2-3 hours.
Having your infusion IV means that a higher dose can be given at
once, which is why you only need to have treatment every 3-4 weeks.
The downside to having IV treatment is that you need to have veins
which can be accessed easily and the side effects mentioned above can
be more noticeable due to the higher dose given in one infusion.
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Some people don’t have great veins to begin with or just may not
like larger needles too much. For these patients subcutaneous
treatment (SC) can be the preferred option. This method is still carried
out with a needle, but a much smaller one which goes into
the fatty layer of tissue under the skin around the abdomen or
upper thighs, rather than into a vein. This means it takes longer for
your body to absorb the liquid and consequently why a smaller, and
more frequent, dose is needed. You may experience some side
effects around the needle site such as swelling, itchiness and redness
although this only lasts for a short while. SC is generally thought
easier to do and, although carried out weekly, infusion time is less
at about 90 minutes. Other advantages for SC therapy are that side
effects are generally less marked, due to the smaller, but more
frequent, doses. It will also give you a more even level of
Immunoglobulins throughout the month.
Differences between IV & SC treatment
Simplified diagram of IgG levels after each infusion of IVIg
Infusion
8g/l
Ideal trough level is maintained above 8g/l.
4 weeks
8 weeks
I Chua
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Simplified diagram of IgG levels after SCIg
Infusion
8g/l
Ideal trough level is maintained above 8g/l.
1 week
2 week
I Chua
Blood testing
Having blood taken is very necessary for us to monitor how your treatment
is going. If you start on replacement therapy we will need to monitor the
levels of immunoglobulins in your bloodstream approximately every three
months. This allows us to find out if you’re getting the right dose, as your
needs may vary depending on the levels of infections you’re having. The
blood will also tell us about your liver function plus an indicator of
infection called the CRP. We may, from time to time, ask you to give some
blood to help in our research projects, but this will only be a small amount
and only when you’re already having blood taken. There is no obligation to
give blood for research and we will always ask for written consent before
doing so.
Psychological treatment
Whilst the majority of people with immunodeficiencies are managing
their condition and the impact on their life well, we know that this is not
true for everybody. There is a link between physical health and mental
wellbeing, and adults with chronic illnesses are at increased risk of
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suffering from depression than the general population. Poor mental
health can also affect an individual’s ability to manage their physical
health. Within the department, we have a psychology service that can
provide short-term, talking therapy to patients with immunodeficiencies,
or support patients to find other more suitable services locally. The
treatment aims for those using the service vary and can include
improvements in mood, general anxiety, specific health anxiety, sleep and
fatigue, and having a space to reflect on the impact the illness has on
their own and other’s lives. We use a practical, cognitive-behavioural
model of treatment which helps individuals to try out different
techniques and skills which can make life easier. If you would like to find
out more about the service or discuss the possibility of an assessment
appointment please ask one of the team.
Jeffrey Modell Foundation
Vicki and Fred Modell established the Jeffrey Modell Foundation (JMF) in
1987, in memory of their son Jeffrey, who died at the age of fifteen,
from complications of primary immunodeficiency. Since 2009, the Royal
Free Hospital is a JMF centre which means that we are dedicated to early
diagnosis, meaningful treatments and, ultimately, cures through research,
physician education, public awareness, advocacy, patient support and
newborn screening.
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Glossary of terms
Antibody: a protein made by B cells which can destroy antigens. Also
known as Immunoglobulins.
Antigen: general term for something that is recognised by your immune
system as harmful and triggers a response. Common antigens can
include particles from bacteria, viruses and fungi.
B cell: a protein and type of lymphocyte. Source of antibodies
(immunoglobulins) which locks on to specific antigens, triggering their
destruction with the help of other immune cells.
Bone marrow: inner part of bone where immune cells and antibodies are
produced.
Intravenous (IV): literally means into a vein and is the most commonly
used route for replacement therapy.
Immunoglobulins: proteins made by B cells. Also known as antibodies.
Three main types: IgM, IgG and IgA. (see main text).
Lymphocyte: a type of white blood cell mostly produced in bone
marrow. Also known as T or B cells. Both are responsible for recognising,
remembering and helping to kill pathogens.
Lymph nodes: Site of antigen and lymphocyte interaction and one of
the sites for antibody production.
Lymph vascular system: carries antibodies and antigens throughout
the body.
Neutrophil: the most common type of phagocyte or ‘cell eater’.
Pathogens: any kind of harmful agent, typically bacteria, viruses or fungi.
Phagocyte: a group of white blood cells which engulf and digest
harmful cells.
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Replacement therapy: term used to describe immunoglobulin infusions.
Subcutaneous (SC): refers to the fatty layer of tissue just under
the skin and is the alternative route for replacement therapy.
Spleen: site of B cell maturation and where blood cells, platelets and
antigens are broken down. Can become enlarged in some patients.
T cell: a protein and type of lymphocyte. Like antibodies, they react to
specific antigens. Comes in 3 types:
• Killer T cells (CD8+): destroy cells invaded by bacteria or viruses but
also cancerous cells and foreign tissue such as transplanted organs.
• Helper T cells (CD4+): activate killer T cells and stimulate B cells to
make antibodies.
• Suppressor T cells: moderate the immune response and prevents the
immune system going into overdrive that could lead to an
‘autoimmune’ response where the body’s own healthy cells are
attacked.
Thymus: small organ located behind the sternum and site of T cell
maturation.
White blood cells: also known as leukocytes, are the main component of
the immune system. The two main types are phagocytes and lymphocytes.
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Useful websites
www.centreforimmunodeficiency.com – This is our own website
linked up with the paediatric service at Great Ormond Street
Hospital. You’ll find plenty of information here, especially about the
specifics of your condition.
www.ucl.ac.uk/immunity-transplantation – This is the website of
the new Institute of Immunity and Transplantation based on the Royal
Free Hospital. You can find lots of information about the research
currently being conducted in immune-related conditions.
www.pidpatients.org – This is the website of the group formed to
represent the interests of patients with Primary Immunodeficiency
(PID) who are managed by the UCL Centre for adult PID at the Royal
Free Hospital. You will find information about PIDs and patient’s
experiences of living with the illness.
www.ipopi.org – This is the International Patient Organisation
for Primary Immunodeficiencies website and has a broad range
of information covering patient issues, drug and treatment
developments, legislation and much more. A very good website.
www.esid.org – Exchange of ideas and information among
doctors, nurses, biomedical investigators, patients and their
families concerned with primary immunodeficiency.
www.ukpin.org.uk – The UK Primary Immunodeficiency Network
(UKPIN) is a multidisciplinary organisation of those caring for
patients with primary immunodeficiencies. UKPIN aims to share
methods of best practice, and to accredit immunology centres
which practice in this way. Please explore these pages to see the
wealth of reports, guidelines and other information available here.
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Contact us
Nurses
Andrew Symes – Clinical Nurse Specialist.
[email protected]
Tel: 020 7830 2140 or blp. 2029 via switchboard (020 7794 0500)
Sarita Workman – Research Sister.
[email protected]
Tel: 020 7794 0500 ext. 33832 or blp. 2831
Irene Wahlberg – Immunology Nurse.
[email protected]
Tel: 020 7794 0500 ext. 34001
Mary Herman – Ward Clerk.
[email protected]
Tel: 020 7794 0500 ext. 36231
Consultants
Dr. Ronnie Chee – Consultant.
[email protected]
Tel: 020 7794 0500 ext. 34519
Dr. Siobhan Burns – Consultant.
[email protected]
Tel: 020 7794 0500 ext. 36662
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Dr. Suranjith Seneviratne – Consultant.
[email protected]
Tel: 020 7794 0500 ext. 34519
Jacqueline Glendinning – Medical Secretary.
[email protected]
Tel: 020 7830 2141
Tel: 020 7794 0500 ext. 34519
Registrars
Dr. Magdalena Dziadzio – Special Registrar.
[email protected]
Tel: 020 7794 0500 ext. 34807 or blp. 1168
Dr. Nisha Verma – Special Registrar.
[email protected]
Tel: 020 7794 0500 ext. 34807 or blp. 1168
Psychologist
Dr. Mari Campbell – Clinical Psychologist.
[email protected]
Tel: 020 7794 0500 ext. 31467
Jeffrey Model Foundation
Paula Freitas – JMF Project Coordinator.
[email protected]
Tel: 020 7794 0500 ext. 34892
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Design and photography by the Medical Illustration Unit, Royal Free & University College Medical School (Hampstead Campus).